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Open Access Research

Multi-walled carbon nanotube instillation impairs pulmonary function in C57BL/6 mice

Xiaojia Wang1*, Pranita Katwa1, Ramakrishna Podila2, Pengyu Chen2, Pu Chun Ke2, Apparao M Rao2, Dianne M Walters3, Christopher J Wingard3 and Jared M Brown1*

Author Affiliations

1 Department of Pharmacology & Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA

2 Department of Physics and Astronomy, Clemson University, Clemson, South Carolina, USA

3 Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA

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Particle and Fibre Toxicology 2011, 8:24  doi:10.1186/1743-8977-8-24

Published: 18 August 2011

Abstract

Background

Multi-walled carbon nanotubes (MWCNTs) are widely used in many disciplines due to their unique physical and chemical properties. Therefore, some concerns about the possible human health and environmental impacts of manufactured MWCNTs are rising. We hypothesized that instillation of MWCNTs impairs pulmonary function in C57BL/6 mice due to development of lung inflammation and fibrosis.

Methods

MWCNTs were administered to C57BL/6 mice by oropharyngeal aspiration (1, 2, and 4 mg/kg) and we assessed lung inflammation and fibrosis by inflammatory cell infiltration, collagen content, and histological assessment. Pulmonary function was assessed using a FlexiVent system and levels of Ccl3, Ccl11, Mmp13 and IL-33 were measured by RT-PCR and ELISA.

Results

Mice administered MWCNTs exhibited increased inflammatory cell infiltration, collagen deposition and granuloma formation in lung tissue, which correlated with impaired pulmonary function as assessed by increased resistance, tissue damping, and decreased lung compliance. Pulmonary exposure to MWCNTs induced an inflammatory signature marked by cytokine (IL-33), chemokine (Ccl3 and Ccl11), and protease production (Mmp13) that promoted the inflammatory and fibrotic changes observed within the lung.

Conclusions

These results further highlight the potential adverse health effects that may occur following MWCNT exposure and therefore we suggest these materials may pose a significant risk leading to impaired lung function following environmental and occupational exposures.

Keywords:
MWCNT; pulmonary fibrosis; pulmonary function; Ccl3; Ccl11; Mmp13; IL-33; Flexivent; Raman spectroscopy